REPORT TO THE GENERAL ASSEMBLY

Transcription

1 REPORT TO THE GENERAL ASSEMBLY PUBLIC ACT AN ACT CONCERNING REVISIONS TO STATUTES RELATING TO THE DEPARTMENT OF PUBLIC HEALTH UMBILICAL CORD BLOOD BANK January 1, 2008 J. Robert Galvin, M.D., M.P.H., Commissioner State of Connecticut Department of Public Health 410 Capitol Avenue P.O. Box Hartford, CT

2 State of Connecticut Department of Public Health Report to the General Assembly Public Act An Act Concerning Revisions to Statutes Relating to the Department of Public Health Umbilical Cord Blood Banks Table of Contents I. Introduction... 3 II. Background III. Request For Information IV. Response to Request For Information V. Summary and Recommendations... 8 V. Appendices A. Public Act 06-77, An Act Designating the Month of November as Lung 10 Cancer Awareness Month and Concerning the Establishment of a Public Umbilical Cord Blood Bank B. Umbilical Cord Blood Bank Ad Hoc Committee Report to the General Assembly.. 13 C. Public Act , An Act Concerning Revisions to Statutes Relating to the Departments of Public Health and Social Services and Town Clerks: Sec D. Request for Information for Establishing a Public Umbilical Cord Blood Operation. 69 Page

3 I. Introduction The General Assembly mandated in Section 77 of Public Act , that on or before October 1, 2007, the Commissioner of Public Health shall request information from one or more umbilical cord blood banks concerning the establishment of a public cord blood collection operation within this State to collect, transport, process and store cord blood units from Connecticut residents for therapeutic and research purposes. The Act mandated the Commissioner to submit a summary of the responses and any recommendations to the Governor and the Public Health Committee by January 1, II. Background Public Act established an ad hoc committee (the Committee) to examine and evaluate the feasibility of (1) establishing a public umbilical cord blood bank for the purpose of collecting and storing umbilical cord blood and placental tissue donated by maternity patients at hospitals licensed in this State, (2) entering into a multi-state public umbilical cord collaboration, and (3) developing a public-private partnership with existing umbilical cord blood banks. Per the Act, the Commissioner of the State Department of Public Health convened the inaugural meeting on July 18, The Committee studied cord blood banking operations in detail, including the critical components of public education, collection, processing and storage, and the sale of cord blood units (CBUs). Based on its information gathering activities, the Committee agreed to the following broad guidelines in addressing the role of the State of Connecticut with respect to establishing a public umbilical cord blood bank: All birthing mothers should be informed about available public and private cord blood donation and banking options in the State. Connecticut should develop viable public cord blood banking options. Connecticut efforts should address the need for racial and ethnic diversity in and unrestricted access to public umbilical cord blood supplies. Connecticut does not need to develop its own public cord blood donation and banking program, and should explore partnerships with existing public and/or private cord blood banks. The collection, transportation, processing and storage of all umbilical cord blood from birthing mothers in Connecticut should be done in accordance with all applicable existing regulatory requirements promulgated by the federal government and by national accreditation bodies. Relevant components of the Connecticut health care delivery community should be fully educated about public and private cord blood banking programs and as appropriate, fully compliant with acceptable standards of practice for the collection of umbilical cord blood. The Committee agreed that the most advantageous approach to providing for collection of CBUs within the State is through a public-private partnership between the State and a cord blood bank that is willing to establish public collection operations within Connecticut to collect CBUs for therapeutic and research use. Because the Committee was not 1 An Act Designating the Month of November as Lung Cancer Awareness Month and Concerning the Establishment of a Public Umbilical Cord Blood Bank. See Appendix A 3

4 tasked with seeking proposals for establishing collection activity, the specific terms of such an arrangement were not determined. However, within the public-private partnership approach, the Committee recommended that the State pursue a solicitation process to seek proposals from existing banks that would contain the following elements: 1. The bank would agree to establish and operate one or more collections sites within the State to collect a targeted number of units to be determined as a part of the process. 2. The collection program would be committed to collection of CBUs that reflect the racial and ethnic and diversity of the State s citizens. 3. The bank may request an investment from the State to support collection, processing and banking. 4. Any requested State support would be offset by a proportional distribution to the State from sales of the CBUs from the partner bank, either out of the bank s general inventory or from the CBUs collected under that State program. 5. The bank would agree to set up operations within six months of the completion of the contract, provided that contracts with collection sites can be identified and negotiated within that time frame. 6. The bank would participate in the federally created Cord Blood Coordinating Center (CBCC) by listing units so that the maximum opportunity for use will be assured. 7. The bank must have a program that provides CBUs for research and will agree to provide units not suitable for therapeutic use to researchers located within Connecticut without charge. 8. The bank must be accredited as a public bank by one of the national accrediting organizations recognized by Health Resources and Services Administration (HRSA). 9. The bank must demonstrate ability to meet applicable Food and Drug Administration requirements. The Committee reported its findings and recommendations to the legislature and to the Office of the Governor on January 5, In response to the January 5, 2007 report and recommendations of the Committee, the General Assembly mandated in Section 77 of Public Act , that on or before October 1, 2007, the Commissioner of Public Health shall request information from one or more umbilical cord blood banks concerning the establishment of a public cord blood collection operation within this State to collect, transport, process and store cord blood units from Connecticut residents for therapeutic and research purposes. III. Request for Information On August 15, 2007, the Department issued a Request for Information (RFI) for Establishing a Public Umbilical Cord Blood Operation 4. The RFI announcement was sent to 23 public and 21 private cord blood banks in the United States. The RFI 2 See Appendix B 3 An Act Concerning Revisions to Statutes Relating to the Departments of Public Health and Social Services and Town Clerks. See Appendix C 4 See Appendix D 4

5 announcement was also posted on the Departments of Public Health and Administrative Services websites. Existing umbilical cord blood banks were asked to: Describe their ability to establish and operate one or more collection sites within the State to collect a target number of cord blood units. Describe their ability to implement collection procedures designed to collect cord blood units that reflect the State s racial and ethnic diversity. Describe their ability to meet the mandate in the law of setting up the cord blood collection operations within six months after execution of a contract with the State, provided that the umbilical cord blood bank is able to negotiate any necessary contracts related to the collection sites within that time frame. Describe their ability to participate in the National Cord Blood Coordinating Center or similar national cord blood inventory center by listing cord blood units in a manner that assures maximum opportunity for use. Describe their program for providing cord blood units for research and agreement to provide cord blood units that are unsuitable for therapeutic use to researchers located within Connecticut at no charge. Describe their ability to maintain national accreditation by an accrediting organization recognized by the federal Health Resources and Services Administration. Describe their program for conducting educational outreach to practitioners, patient donors and hospitals. Banks were also asked to provide company profile information which will be used to gain a better understanding of the nature and the capability of each respondent including their expertise in umbilical cord blood banking and their experience with state government. Finally, banks were asked to describe their experience and approach to establishing a public/private partnership regarding the collection, transporting, processing, storing and sale of cord blood units collected within the State. The RFI submission date was September 26, IV. Responses to Request for Information Four existing blood bank companies responded to the RFI: Bergen Community Regional Blood Center (Elie Katz Umbilical Cord Blood Program Division); Oradell, New Jersey Cryobanks International, Inc.; Altamonte Springs, Florida Lifeline Cryogenics; Stamford, Connecticut New England Cryogenic Center/New England Cord Blood Bank/New England Cell Repository; Newton, Massachusetts The respondent included two private blood bank providers and two public/private blood banks. A summary of the responses to the RFI follows: A. Ability to establish and operate one or more collection sites within the State to collect a target number of cord blood units. 5

6 All respondents were experienced in setting up one or more collection sites in multiple locations, with six to twelve years experience in cord blood banking. Two companies currently work with many of the birthing hospitals in Connecticut, while the other respondents have banking experience in multiple states and jurisdictions. One bank is the designated public cord blood bank by the State of New Jersey, and collects cord blood for donation into the public bank from three states. B. Ability to implement collection procedures designed to collect cord blood units that reflect the State s racial and ethnic diversity. Each respondent identified the need for targeted collection activities to address the racial diversity of its registered cord blood units. One bank provided data on the diversity of its current cord blood units and also provided in depth information regarding long term strategies to increase the diversity of its donor pool. One respondent described its efforts to create a diverse bank through the establishment of a national donor program, and two respondents identified the need for target sites for collecting from a diverse pool. C. Ability to meet the mandate in the law of setting up the cord blood collection operations within six months after execution of a contract with the State. Three of the four banks indicated that meeting the six month time frame was reasonable, with one bank noting that the six month time frame is both realistic and timely. One bank failed to discuss or commit to meeting this time frame. D. Ability to participate in the National Cord Blood Coordinating Center or similar national cord blood inventory center. All respondents noted the importance of participating in national and/or international efforts to maximize the use of public cord blood units. One bank committed to participating in and following the recommendations of the National Cord Blood Coordinating Center, and one bank noted the importance of registering in the National Cord Blood Coordinating Center or the National Cord Blood Inventory. One respondent indicated that all current public cord blood units are registered with the National Marrow Donor Program or listed on the Bone Marrow Donor Worldwide database, while the fourth indicated that it has listed over 9,500 cord blood units on various registries including the National Marrow Donor Program and the Caitlin Raymond International Registry. E. Ability and experience providing cord blood units for research and agreement to provide cord blood units that are unsuitable for therapeutic use to researchers located within Connecticut at no charge. Each of the responding banks indicated that currently collected umbilical cord blood units which are unsuitable for therapeutic use are made available to qualified researchers. One respondent indicated that the research should be peer reviewed, and a second indicated that its policy prohibits using these units for controversial or cosmetic purposes. 6

7 While emphasizing the need for appropriate informed consent, three of the banks indicated a willingness or intent to donate unsuitable cord blood units to Connecticut researchers. The other bank noted that it currently shares unsuitable cord blood units with researchers from throughout the United States without specifying its agreement to share such units with Connecticut researchers. F. Describe their ability to maintain national accreditation by an accrediting organization recognized by the federal Health Resources and Services Administration. All respondents described their current national accreditations, certifications and registrations from a variety of national organizations and agencies. Three of the respondents noted they held multiple state licenses. G. Describe their program for conducting educational outreach to practitioners, patient donors and hospitals. Three respondents described their current or planned efforts for conducting educational outreach to practitioners, donors and hospitals. One bank offers educational and recruitment materials in Spanish, Mandarin, Arabic, Hindi, and Korean, and uses bilingual collections specialists to conduct hospital based on-site educational sessions. Another bank provides in facility tours to physicians, nurses, donors and hospital personnel, hospital based in-service training to instruct labor and delivery staff, and conducts educational outreach at obstetrical offices. A third bank described current hospital based lectures and grand rounds targeting physicians, nurses and student, and regular open houses for medical personnel and the general public. One bank described their training as the only dedicated cord blood processing training program in existence. All of the respondents stressed the need for an active targeted educational outreach program. H. Experience with Public/Private Partnerships All respondents provided information regarding their relationships with existing facilities, providers and jurisdictions, and their plans for establishing or expanding public/private partnerships with state institutions. Two banks described their specific experiences partnering with state governments. One bank, currently designated by executive order as a state cord blood facility in New Jersey, included a description of its active relationship with the state health department with respect to educational efforts and the development of medical emergency protocols. I. Other Considerations Each of the respondents indicated an interest in partnering with the State of Connecticut in the establishment of a public umbilical cord blood bank. The RFI did not impose any additional criteria, and two of the respondents left future considerations or parameters for partnership up to future negotiations while noting reasons why their experiences and expertise would be of benefit. The remaining banks provided more detailed information concerning possible partnering opportunities. 7

8 One respondent provided two scenarios for partnering. In scenario one, the State would contract with the bank to operate the bank. In the second scenario, the respondent would contract with the State to develop and provide a turnkey operation which Connecticut would operate independently or with the assistance of the contractor. Another bank identified three ways the State could support the development of a successful public umbilical cord banking program; a statewide educational campaign led by the Department of Public Health, development of a coalition of state leaders representing the ethnic diversity of the State, and/or through financial support. V. Summary and Recommendations Public Act , Sec. 77, mandated that on or before October 1, 2007, the Commissioner of Public Health shall request information from one or more umbilical cord blood banks concerning the establishment of a public cord blood collection operation within this State to collect, transport, process and store cord blood units from Connecticut residents for therapeutic and research purposes. On August 15, 2007, the Department issued the attached Request for Information (RFI), outlining the type of information being solicited from vendors and including guidelines for content and format of responses. Four current cord blood banks responded to the RFI expressing their interest in partnering with the State of Connecticut on the development of a public cord blood bank. Two public/private banks responded, including a bank designated by the State of New Jersey as a public umbilical cord blood bank. Two private banks interested in expanding into the public banking arena, including the only cord blood bank in Connecticut, also expressed their interest. All banks were experienced in setting up and operating multiple collection sites, had current or planned strategies and activities addressing the need for collecting units that reflected the State s ethnic and racial diversity. Generally, respondents indicated the ability to set up operation within six months of executing a contract with the State, to participate in national cord blood inventory centers, to make units unsuitable for therapy available to researchers in Connecticut, and to maintain national accreditation, registration, licensing or other credentialing standards. All respondents stressed the need for educational outreach efforts to practitioners, donors and hospitals and stressed as critical the need of establishing a public bank reflecting the State s ethnic and racial diversity. One bank identified public education as an area where the State of Connecticut could take the lead through its Department of Public Health. Two of the respondents have a history of developing public/private partnerships, and the same banks provided information concerning possible roles for the State of Connecticut. While only one respondent mentioned financial support as a consideration for establishing a successful public/private cord blood banking operation, it is clear that there are significant costs associated with each step of the process, including education, recruitment, collection, testing, processing and long term storage. 8

9 It is clear that there is interest in both the private and public sector blood banking communities with respect to partnering with the State of Connecticut in establishing a public umbilical cord blood bank. The most significant, unanswered question is the extent to which the State would need to provide start up or on-going financial support to ensure the success of this effort. Since this question was not addressed in the legislation or the RFI, it is recommended that the Public Health Committee of the General Assembly invite representatives of one or more of the responding banks to make oral presentations before the Committee in order to provide more in depth information concerning its response, including but not limited to a discussion of any necessary State financial support. It is further recommended that the State consider initiating an active targeted educational outreach program to practitioners, donors and hospitals. 9

10 APPENDIX A Public Act 06-77, An Act Designating the Month of November as Lung Cancer Awareness Month and Concerning the Establishment of a Public Umbilical Cord Blood Bank 10

11 Public Act No AN ACT DESIGNATING THE MONTH OF NOVEMBER AS LUNG CANCER AWARENESS MONTH AND CONCERNING THE ESTABLISHMENT OF A PUBLIC UMBILICAL CORD BLOOD BANK. Be it enacted by the Senate and House of Representatives in General Assembly convened: Section 1. Subsection (a) of section 10-29a of the 2006 supplement to the general statutes is amended by adding subdivision (51) as follows (Effective October 1, 2006): (NEW) (51) Lung Cancer Awareness Month. The Governor shall proclaim the month of November to be Lung Cancer Awareness Month to heighten public awareness of the fact that lung cancer is the leading cause of cancer death of both men and women in the United States. Suitable exercises shall be held in the State Capitol and elsewhere as the Governor designates for the observance of the month. Sec. 2. (Effective from passage) (a) The Commissioner of Public Health, in consultation with the Stem Cell Research Advisory Committee established pursuant to section 19a-32f of the 2006 supplement to the general statutes, shall establish an ad hoc committee to examine and evaluate the feasibility of (1) establishing a public umbilical cord blood bank for the purpose of collecting and storing umbilical cord blood and placental tissue donated by maternity patients at hospitals licensed in this state, (2) entering into a multistate public umbilical cord collaboration, and (3) developing a public-private partnership with existing umbilical cord blood banks. The committee shall hold its first meeting not later than sixty days after the effective date of this section. Other topics may be included at the discretion of either the commissioner or the Stem Cell Research Advisory Committee. 11

12 (b) (1) The ad hoc committee shall be appointed by the Commissioner of Public Health and shall consist of the Commissioners of Public Health and Economic and Community Development, or their designees; one member of the Stem Cell Research Advisory Committee established pursuant to section 19a-32f of the 2006 supplement to the general statutes, selected by the Stem Cell Research Advisory Committee; one researcher from a private institution of higher education in the state; one researcher from a public institution of higher education in the state; one representative of an educational and business support network organization for bioscience in the state; one individual who is a member in good standing of the American Association of Blood Banks, with expertise in umbilical cord blood banking and the Food and Drug Administration's federal safety standards for umbilical cord blood banks; one individual with multiple years of experience in establishing, executing and administering an umbilical cord blood registry. The Commissioner of Public Health shall serve as chairperson of the committee. (2) The Commissioner of Public Health, in consultation with the Stem Cell Research Advisory Committee, may expand the membership of the ad hoc committee to include additional members if either decides such expansion would be useful. (c) On or before January 5, 2007, the Commissioner of Public Health shall submit, in accordance with section 11-4a of the general statutes, the results of the examination, along with any recommendations, to the Governor and the joint standing committee of the General Assembly having cognizance of matters relating to public health. Approved May 30,

13 APPENDIX B Umbilical Cord Blood Bank Ad Hoc Committee Report to the General Assembly 13

14 REPORT TO THE GENERAL ASSEMBLY Public Act AN ACT CONCERNING THE ESTABLISHMENT OF A PUBLIC UMBILICAL CORD BLOOD BANK January 5, 2007 J. Robert Galvin, M.D., M.P.H., Commissioner State of Connecticut Department of Public Health 410 Capitol Avenue P.O. Box Hartford, CT

15 Connecticut Department of Public Health Umbilical Cord Blood Ad Hoc Committee Report to the Office of the Governor and the General Assembly January 5, 2007 Public Act No AN ACT DESIGNATING THE MONTH OF NOVEMBER AS LUNG CANCER AWARENESS MONTH AND CONCERNING THE ESTABLISHMENT OF A PUBLIC UMBILICAL CORD BLOOD BANK. Table of Contents Page I. Executive Summary 2 II. Introduction 5 A. Charge to the Committee 5 B. Overview of Developments in Cord Blood Banking 5 III. Use of Hematopoietic Cells in Transplantation 6 A. Overview 6 B. Overview of the Therapeutic Use of Cord Blood 8 1. Umbilical Cord Blood Transplants in Pediatrics 8 2. Umbilical Cord Blood Transplants in Adults 9 IV. Cord Blood Banking 10 A. Umbilical Cord Blood Banks 10 B. Banking Operations Public Education Collection Processing and Storage Sale of Cord Blood Units 12 V. Economics of Cord Blood Banking 12 A. Demand for Unrelated Transplants 12 B. Supply of Public Cord Blood Units 13 C. Cost of Banking 14 VI. Federal Involvement in Cord Blood Banking 15 A. Development of a National Program 15 B. Food and Drug Administration Regulation 17 VII. Committee Deliberations 18 VIII. Committee Findings 19 IX. Committee Recommendations 22 X. Appendices A. Public Act No B. Committee Membership 27 C. Other State Regulatory Activities 29 D Stem Cell Therapeutic and Research Act 0f E. Pro Forma 42 15

16 Report of the Ad Hoc Committee Concerning the Establishment of a Public Umbilical Cord Blood Bank January 5, 2007 Executive Summary Public Act (the Act) established an ad hoc committee (the Committee) to examine and evaluate the feasibility of (1) establishing a public umbilical cord blood bank for the purpose of collecting and storing umbilical cord blood and placental tissue donated by maternity patients at hospitals licensed in this state, (2) entering into a multi-state public umbilical cord collaboration, and (3) developing a public-private partnership with existing umbilical cord blood banks. Per the Act, the Commissioner of the State Department of Public Health appointed members to the Committee 6 and convened the inaugural meeting on July 18, During subsequent meetings held on September 11, 2006, October 30, 2006, December 5, 2006, and December 27, 2006, the Committee reviewed current federal, state and private banking programs and regulatory requirements, and received testimony from state, regional and national experts on cord blood banking practices and the clinical uses of cord blood, including a review of the use of hematopoietic cells in transplantations, and an overview of the therapeutic use of cord blood transplants in the pediatric and adult populations. The need for increased racial and ethnic diversity of the cord blood supply was reviewed at length both in terms of the Connecticut population and the national cord blood supply. Once considered medical waste, the umbilical cord and placenta are now known to contain adult stem cells that can be used to provide a life saving stem cell transplant for patients with various malignancies. Because of its biology, the adult stem cells contained in cord blood do not have to be as closely tissue matched as do the adult stem cells obtained from the other two sources of adult stem cells, namely bone marrow and peripheral blood. This biological finding makes collection and provision of cord blood stem cells a great benefit to ethnic minorities and other patient groups who are currently unable to obtain an adequate match for a transplant using bone marrow or peripheral blood stem cells. Some of the benefits of a Cord Blood Collection and Storage Program include: Ease of collection. Less need for an identical tissue (HLA) match between donor and recipient. Permits ethnic and other minorities to access adult stem cells for a life saving transplant. Cord blood transplants are successful for both children and adults. 5 see Appendix A 6 see Appendix B 16

17 Cord blood stem cells have potential for use in many emerging medical areas that require tissue growth such as manufacture of blood vessels for patients with heart disease. The Committee studied cord blood banking operations in detail, including the critical components of public education, collecting cord blood units (CBU), processing and storage, and the sale of cord blood units. The economics of cord blood banking were studied and discussed in depth. The Committee identified the three major cost elements associated with establishing and operating a public bank as the capitol costs for the processing and storage facility, the labor costs associated with collecting and processing, and the costs of testing the unit for transfusion-related disease markers and donor markers of genetic diseases. Based on its information gathering activities, the Committee agreed to the following broad guidelines in addressing the role of the State of Connecticut with respect to establishing a public umbilical cord blood bank: All birthing mothers should be informed about available public and private cord blood donation and banking options in the state. Connecticut should develop viable public cord blood banking options. Connecticut efforts should address the need for racial and ethnic diversity in and unrestricted access to public umbilical cord blood supplies. Connecticut does not need to develop its own public cord blood donation and banking program, and should explore partnerships with existing public and/or private cord blood banks. The collection, transportation, processing and storage of all umbilical cord blood from birthing mothers in Connecticut should be done in accordance with all applicable existing regulatory requirements promulgated by the federal government and by national accreditation bodies. Relevant components of the Connecticut health care delivery community should be fully educated about public and private cord blood banking programs and as appropriate, fully compliant with acceptable standards of practice for the collection of umbilical cord blood. The Committee agrees that the most advantageous approach to providing for collection of CBUs within the state is through a public-private partnership between the state and a public cord blood bank that is willing to establish public collection operations within Connecticut to collect CBUs for therapeutic and research use. The chief advantage of this approach is that it provides a mechanism that will encourage collections within the state at the earliest possible time frame while avoiding the need to invest significantly in the development of the infrastructure to create a new banking facility. There are a number of approaches to a public-private partnership. The Committee believes that the best model would be one that provides for financial support from the state to encourage collection activity coupled with an expectation of a return to the state of some or all of the sale proceeds of the CBUs collected within the state. Because the Committee was not tasked with seeking proposals for establishing collection activity, the specific terms of such an arrangement have not been determined. However, within the 17

18 public-private partnership approach, the Committee recommends that the state pursue a solicitation process to seek proposals from existing banks that would contain the following elements: 10. The bank would agree to establish and operate one or more collections sites within the state to collect a targeted number of units to be determined as a part of the process. 11. The collection program would be committed to collection of CBUs that reflect the racial and ethnic and diversity of the state s citizens. 12. The bank may request an investment from the state to support collection, processing and banking. 13. Any requested state support would be offset by a proportional distribution to the state from sales of the CBUs from the partner bank, either out of the bank s general inventory or from the CBUs collected under that state program. 14. The bank would agree to set up operations within six months of the completion of the contract, provided that contracts with collection sites can be identified and negotiated within that time frame. 15. The bank would participate in the federally created Cord Blood Coordinating Center (CBCC) by listing units so that the maximum opportunity for use will be assured. 16. The bank must have a program that provides CBUs for research and will agree to provide units not suitable for therapeutic use to researchers located within Connecticut without charge. 17. The bank must be accredited as a public bank by one of the national accrediting organizations recognized by Health Resources and Services Administration (HRSA). 18. The bank must demonstrate ability to meet applicable Food and Drug Administration requirements. It is anticipated that CBBs will be willing to establish collection sites within the state under these terms. The advantages to the state in such an arrangement are: 1. Avoid the cost of establishing its own facilities. 2. Move quickly to establish collections within the state by taking advantage of the existing programs of public cord blood banks. 3. Recognizing that some investment may be necessary to encourage collection within the state, the program would hope to recoup some or all of the investment overtime by receiving a portion of the fees charged within units are sold for therapeutic or research purposes. 4. Through its participation, Connecticut will be able to provide for collection in an equitable manner for its citizens. The Committee considered the option whereby the state would establish a banking operation under state ownership and control but felt that this option was not desirable as it represented the highest cost and greatest risk to the state. In addition, it would take a considerable amount of time to set up. Since nongovernmental entities have already 18

19 created expertise and capacity for public banking, the state could avoid the cost and risk but still accommodate the desire for public banking within the state through a publicprivate partnership. Likewise, the Committee does not recommend pursuing a multi-state approach at this time. While this approach may have advantages in providing an opportunity to share the risk of investment and operations, it would require significant effort to enlist and develop such an arrangement with other states, even if the reception to such an idea were welcome. However, the state should be prepared to respond to overtures along these lines should interest be expressed as it pursues its own track, consistent with the recommendations of the Committee, if adopted. 19

20 II. INTRODUCTION A. Charge to the Committee Public Act 06-77, AN ACT DESIGNATING THE MONTH OF NOVEMBER AS LUNG CANCER AWARENESS MONTH AND CONCERNING THE ESTABLISHMENT OF A PUBLIC UMBILICAL CORD BLOOD BANK (The Act) was enacted on May 30, 2006 in Connecticut. Concerned about the lack of choices for public cord banking offered to birthing women in Connecticut and recognizing the therapeutic and research importance of umbilical cord blood, the General Assembly tasked the Department of Public Health, through its Commissioner, to convene an ad hoc committee (the Committee) to study the feasibility of establishing a public umbilical cord bank in Connecticut for the purpose of collecting and storing umbilical cord blood and placental tissue donated by maternity patients at hospitals licensed in the state. The Committee was also tasked with addressing the potential for a multi-state public umbilical cord partnership, and the potential for a developing a public-private partnership with existing umbilical cord blood banks. The Committee was mandated to report its findings and recommendations to the legislature and to the Office of the Governor by January 5, B. Overview of Developments in Cord Blood Banking According to the National Institute of Medicine 7, stem cells are a primitive cell type that are found in all types of animals, and that are different from all other types of cells. All stem cells share three common traits: they are capable of dividing and of self-renewal for periods of time; they are unspecialized; and they have the ability to develop into specialized cell types through the process of differentiation. The National Institute of Medicine classifies three types of stem cells based on their ability to differentiate: Totipotent cells - capable of giving rise to all the different types of cells within the body as well gestational support structures like the placenta. Examples are the fertilized egg (zygote) and the individual cells of the cleaving zygote prior to the fifth cellular division (blastomeres). Pluripotent cells - capable of giving rise to all the different types of cells within the body but not the gestational support structures. An example is embryonic stem cells. Multipotent cells - capable of giving rise to a limited number of different cell types. Examples are blood stem cells and neural stem cells. Multipotent stem cells are also called "adult stem cells" or "tissue-specific stem cells". Due to the diagnostic and therapeutic potential of pluripotent stem cells and the current federal restrictions on funding research with non-federally approved pluripotent, human embryonic stem cells, the State of Connecticut funds and administers its own Stem Cell 7 Institute of Medicine: Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program, (National Acadamies Press, 2005) 20

21 Research Program. Additional information on this program can be found on the state Department of Public Health s web site at This report focuses on a specific multipotent stem cell, the Hematopoietic Progenitor Cell (HPC), and more specifically, an adult HPC obtained from umbilical cord blood (UCB). To reiterate, even though these are cord blood cells from a newborn, biologically they are classified as adult HPCs. HPCs can differentiate into the vast array of normal blood cells, including the cellular components comprising the blood and the immune system. HPCs can be obtained from a number of different sources, including bone marrow, peripheral blood, and from UCB collected from the placentas of recently delivered infants. HPCs have been transplanted to treat a number of blood diseases, selected metabolic disorders and immunodeficiencies, and sickle cell anemia. As early as 1982, umbilical cord blood was identified as containing hematopoietic progenitor cells suitable for transplants 8. HPCs obtained from umbilical cord blood appear to have some advantage over HPCs obtained from bone marrow or donor blood. According to the National Institute of Health, cord blood HPCs appear less mature that than those from other sources, so their transplantation results in a lower risk of graftversus-host disease. Cord blood HPCs are readily available, and collection is painless and safe 9. The first UCB transplant in the United States was reported in Since then, for the thousands of patients each year needing a bone marrow transplant but lacking an appropriate match, or for those patients too sick to wait for a lengthy screening, identification and harvesting program, cord blood derived HPCs have offered a viable option for life saving therapies. According to the National Cord Blood Program 10, there have been more than 6,000 cord blood transplants throughout the world to date. Given the therapeutic results, there appears to be an ever- increasing number of therapeutic applications for cord blood transplant treatment of thousands of patients. III. USE OF HEMATOPOIETIC CELLS IN TRANSPLANTATION Overview Diseases occurring within the blood or hematopoietic system have long plagued mankind. Skeletal remains from the fourth century showed the terminal stages of multiple myeloma 11, a rare form of bone marrow cancer. The recognition of acute myeloid leukemia (AML) as a discrete, clinical entity came in 1827 by the French surgeon Alfred Velpeau. The term leukemia was coined by Rudolf Virchow, in Cellular Characteristics of Cord Blood and Cord Blood Transplantation, Broxmeyer, H.E., Hhttp:// 10 Hhttp:// 11 Greaves M. Cancer: The Evolutionary Legacy (Oxford University Press, Oxford, 2000). 12 Henderson ES. in Leukemia (eds. Henderson, E. S., Lister, T. A. & Greaves, M. F.) 1-7 (W.B.Saunders, Philadelphia, 1996). 21

22 Various regimens for treating leukemia were attempted early on but it was not until World War I that chemicals known as nitrogen mustards including mustard gas, were noted to have the ability to destroy blood-producing bone marrow cells. Thus, it became possible to destroy diseased blood tissue in conditions such as leukemia. While nitrogen mustards and other compounds were very potent at eliminating diseased blood tissue, unfortunately they also destroyed healthy blood tissue. Under-treating patients left them with residual disease that quickly relapsed. Overly aggressive chemotherapy, however, left patients anemic, bleeding-prone, and susceptible to infections provided they survived the treatment at all. The ability to replace blood-producing tissues was thus seen as having strong therapeutic potential. Indeed, HPC transplant had the potential to offer a true lasting cure for the patient suffering from hematological malignancies and other blood diseases. In 1957, E. Donnall Thomas reported on his laboratory s early attempts at a procedure to infuse bone marrow cells from one person into another (allogeneic transplantation) 13. By the 1980 s, bone marrow transplantation had become an effective therapy offered in many medical centers worldwide, and in 1990, Dr. E. Donnall Thomas received the Nobel Prize for pioneering the field of bone marrow transplantation 14. Today, blood stem cell transplantation is offered as a therapeutic maneuver for a wide variety of hematologic, metabolic and genetic diseases 15. It was initially thought that only bone marrow could provide the HPC needed for transplantation. We have now learned that HPC can be recovered from other sources as well. A second source is from peripheral blood. This requires that the donor be stimulated with a drug (G-CSF a white cell stimulating factor) that stimulates the bone marrow to release its stem cells into the peripheral blood where they can be collected by an automated blood collection device known as an apheresis machine. Such machines are used daily at blood centers worldwide to collect blood products such as platelets for transfusion. More recently, it was discovered that blood from the umbilical cord and placenta contain valuable HPCs. Once viewed as postpartum medical waste, umbilical cord or placental blood is now highly valued for its HPCs. Indeed, as will be discussed below, cord blood can be used to transplant adults as well as children. Thus, we now recognize three primary sources of adult HPCs for transplantation: bone marrow G-CSF-stimulated peripheral blood cord blood While it has improved the lives of thousands of people, many more still have been unable to take advantage of this life-extending therapy for a variety of reasons. The inability to locate a suitably matched tissue donor stands out above the rest. While there are many genes that are key to the immune recognition process involved in matching, three genes are known to be of central importance. They are HLA-A, HLA-B, and HLA-DR. These genes are inherited by each of us from our parents. We have six copies of HLA genes in 13 E.D. Thomas, H.L. Lochte, Jr., W.C. Lu and J.W. Ferrebee, N. Engl. J. Med. 257, (1957)

23 total, two HLA-A genes, two HLA-B's, and two more HLA-DR's, one of each from our mother and one of each from our father. This is why the best match is often called a 6/6 ( six out of six ) match. Today, using the most sophisticated methods of HLA typing, additional so-called minor antigen variations have been identified. Indeed, now the best match is viewed as a 10 out of 10 antigen match. The better the match, the more likely it is that the transplant or graft will not fail. The greatest chances for finding a good match are with one's own siblings, especially if one has an identical twin, since identical twins share the exact same genetic makeup. Tissue matching refers to a genetic match between the tissue of the patient and that of the donor, so that the patient's body does not reject the needed transplant as being "foreign", thus leading to tissue rejection, i.e., graft failure. There is another complication that may occur as a consequence of tissue rejection, known as "graft versus host disease" or GvHD. In this potentially lethal condition, immune cells present in the transplanted tissue attack the patient's body. In a sense, the graft actually rejects the patient. The crux of the problem with HLA matching is that the HLA antigen system is incredibly diverse (pleomorphic). Due to a very large number of variations of these antigens known as alleles, enormous numbers of different combinations of these important antigens exist. This explains why the HLA antigen system is so complex. Various ethnic groups tend to share similar alleles. However intermarriages and the mobility of the earth s population have led to a global spreading of the HLA genes. Thus, if someone from a particular ethnic group does not have many blood relatives, their chances of finding a 6/6 match are slim unless a donor registry is large and diverse enough to include people from all over the globe where their ancestors may have migrated or intermarried. For the reasons described above, it is possible that a match might be found in another more distantly related family member or even a total stranger. Generally, however, a good 6/6 (or 10/10) HLA antigen match becomes less likely the more distantly related the donor is to the patient. Of course, a person does not have to be related to the patient at all. While a stranger can also be a match, there is simply a lower probability of such a match occurring with an unrelated donor, compared to a close biological family member. This is why national and international bone marrow donor databases such as that maintained by the National Marrow Donor Program are so important 16. Thus, a donor on a registry in Spain, might just be a match for a patient in Connecticut- or vice versa. Despite such registries, however, vast donor shortfalls remain. As many as 2/3 of all patients needing such a transplant will be unable to locate a suitable donor and this figure may be even worse among certain ethnic groups 17. Alternative sources for transplantable blood-forming tissue have been sought. One such resource is umbilical cord blood, also known as placental blood see Lensch and Daley "Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells" Blood Apr 1;107(7): and references therein. 23

24 B. Overview of the Therapeutic Use of Cord Blood 1. Umbilical Cord Blood Transplants in Pediatrics: Umbilical cord blood (UCB) has been used as an alternative source of hematopoietic stem cells (HSC) for transplantation in the pediatric setting for over a decade. As discussed, HPC transplantation has been used effectively in the setting of both malignant and nonmalignant diseases. Umbilical cord blood has a large number of blood stem cells 18. At birth, this blood is discarded along with the umbilical cord and the placenta. Recognizing that this discarded material had the potential for great clinical importance, studies began to characterize its blood-forming activity and applicability to clinical transplantation. The first successful blood-forming tissue transplant using umbilical cord blood as a cellular source, i.e., a cord blood transplant, was performed by Dr. Eliane Gluckman of the Hospital Saint-Louis of Paris in The patient, a child suffering from a rare genetic blood disease Fanconi anemia, is today a young man alive and well almost twenty years post-transplant. He is being followed by Dr. Joanne Kurtzberg of Duke University. Following an invitation, Dr. Kurtzberg came to Connecticut to address the Cord Blood Committee and she provided valuable input into the Committee s charges. UCB Transplant Survival is influenced by several variables which include: donor type (related family member versus unrelated donor registry member) primary disease (malignant vs. nonmalignant disease) HLA match (see above) number of stem cells (dose) infused 20 Data have shown that unrelated UCB transplants in children can be successful with reported disease free survival ranging from 29% to 85% 21. For adult bone marrow transplantation, generally, the closer the HLA antigen match between donor and recipient the better is the transplant outcome. However, UCB transplantation has been shown to be successful even when the patient and cord blood donor are mismatched at 2 antigens (i.e. a 4/6 match). If the biology will allow a successful UCB transplant even with a mismatch at 2 of the 6 HLA antigen sites, this would allow more donors to be acceptable and available as a match for patients in need of a transplant. Such a scenario would expand the donor pool considerably and increase the number of recipients who could receive a life saving UCB transplant. It has been estimated that approximately 80% of pediatric patients who undergo an unrelated UCB transplant receive a mismatched UCB unit Lensch and Daley "Origins of mammalian hematopoiesis: in vivo paradigms and in vitro models" Curr Top Dev Biol. 2004;60: Gluckman E. et al., "Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling" N Engl J Med Oct 26;321(17): Brunstein CG, Wagner JE. Umbilical cord blood transplantation and banking. Ann Rev Med 2006; 57: Balen KK. New trends in umbilical cord blood transplantation. Blood 2005;